Osteosarcoma in Children: Not Only Chemotherapy

Argenziano, Maura; Tortora, Chiara; Pota, Elvira; Paola, Alessandra Di; Martino, Martina Di; Leva, Caterina Di; Pinto, Daniela Di

doi:10.3390/ph14090923

Cited by 17 publications

(23 citation statements)

References 168 publications

(296 reference statements)

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“…TME of osteosarcoma is a highly dynamic environment composed of bone cells, immune cells, matrix, vascular cells, several releasing molecules and blood vessels. 21 By understanding the TME of osteosarcoma and its relationship with immunoreactivity, a better clinical trial of immunotherapy can be designed to hopefully improve the prognosis of patients with osteosarcoma. 22 In the present study, we explored three TME subtypes in osteosarcoma based on 29 Fges that comprehensively describe TME, which had not been reported in previous osteosarcoma studies.…”

Section: Discussionmentioning

confidence: 99%

Tumor microenvironment phenotypes and prognostic evaluation tools for osteosarcoma characterized by different prognostic outcomes and immunotherapy responses

Tu¹,

Chen³

et al. 2023

The Journal of Gene Medicine

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BackgroundThe physiological and immunological characteristics of the tumor microenvironment (TME) have a profound impact on the effectiveness of immunotherapy. The present study aimed to define the TME subtype of osteosarcoma according to the signatures representing the global TME of the tumor, as well as create a new prognostic assessment tool to monitor the prognosis, TME activity and immunotherapy response of patients with osteosarcoma.MethodsThe enrichment scores of 29 functional gene expression signatures in osteosarcoma samples were calculated by single sample gene set enrichment analysis (ssGSEA). TME classification of osteosarcoma was performed and a prognostic assessment tool was created based on 29 ssGSEA scores to comprehensively correlate them with TME components, immunotherapy efficacy and prognosis of osteosarcoma.ResultsThree TME subtypes were generated that differed in survival, TME activity and immunotherapeutic response. Four differentially expressed genes between TME subtypes were involved in the development of prognostic assessment tools. The established prognosis assessment tool had strong performance in both training and verification cohorts, could be effectively applied to the survival prediction of samples of different ages, genders and transfer states, and could well distinguish the TME status of different samples.ConclusionsThe present study describes three different TME phenotypes in osteosarcoma, provides a risk stratification tool for osteosarcoma prognosis and TME status assessment, and provides additional information for clinical decision‐making of immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Tumor microenvironment phenotypes and prognostic evaluation tools for osteosarcoma characterized by different prognostic outcomes and immunotherapy responses

Tu¹,

Chen³

et al. 2023

The Journal of Gene Medicine

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“…OS is the most prevalent malignant bone tumor in childhood characterized by a high rate of metastasis [ 132 , 133 , 134 , 135 , 136 ]. Ewing’s sarcoma is the second most frequent and highly aggressive bone tumor in childhood [ 137 ].…”

Section: Bone Loss In Ccs With a Different Cancer Diagnosismentioning

confidence: 99%

Osteoporosis in Childhood Cancer Survivors: Physiopathology, Prevention, Therapy and Future Perspectives

Tortora

Paoletta

Marrapodi

et al. 2022

Cancers

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The improvement of chemotherapy, radiotherapy, and surgical interventions, together with hematopoietic stem cell transplantation, increased childhood cancer survival rate in the last decades, reaching 80% in Europe. Nevertheless, anti-cancer treatments are mainly responsible for the onset of long-term side effects in childhood cancer survivors (CCS), including alterations of the endocrine system function and activity. In particular, the most frequent dysfunction in CCS is a metabolic bone disorder characterized by low bone mineral density (BMD) with increased skeletal fragility. BMD loss is also a consequence of a sedentary lifestyle, malnutrition, and cancer itself could affect BMD, thus inducing osteopenia and osteoporosis. In this paper, we provide an overview of possible causes of bone impairment in CCS in order to propose management strategies for early identification and treatment of skeletal fragility in this population.

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“…Osteosarcoma (OS), which mainly occurs in children and adolescents, is a type of malignant bone tumor characterized by rapid development, a low degree of differentiation, and high metastases. , The 5-year survival rate of OS patients has gained 60–70% owing to progress in diagnosis, surgical protocols, and chemotherapeutic drugs. − Nevertheless, after the development of metastases, the 5-year survival rate sharply decreases to less than 20%. , The gold standard for OS therapy is neoadjuvant chemotherapy, in which patients receive preoperative chemotherapy to reduce the tumor size, surgery to remove the tumor and fill the defects with implants, and postoperative chemotherapy to prevent recurrence. − However, chemotherapy causes many side effects such as a decreased number of blood cells, damage to the immune system, and, most important, inhibition of bone regeneration around the prosthesis, which can induce implant failure. Therefore, the design and construction of implants with antitumor properties, which reduce the need for postoperative chemotherapy, and simultaneously, enhanced bone reconstruction, would be of great significance for OS therapy.…”

Section: Introductionmentioning

confidence: 99%

Molecular Mechanism Underlying the Action of a Celastrol-Loaded Layered Double Hydroxide-Coated Magnesium Alloy in Osteosarcoma Inhibition and Bone Regeneration

Cheng,

Shao,

Yin

et al. 2023

ACS Biomater. Sci. Eng.

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Osteosarcoma (OS) is a malignant bone tumor that threatens human health. Surgical removal of the tumor and followed by implantation with a graft is the golden standard for its clinical treatment. However, avoiding recurrence by enhancing the antitumor properties of the implants and improving osteogenesis around the implants remain a challenge. Here, we developed a layered double hydroxide (LDH)-coated magnesium (Mg) alloy and loaded it with celastrol. The celastrol-loaded Mg alloy exhibited enhanced corrosion resistance and sustained release of celastrol. In vitro cell culture suggested that the modified Mg alloy loaded with an appropriate amount of celastrol significantly inhibited the proliferation and migration of bone tumor cells while having little influence on normal cells. A mechanistic study revealed that the celastrol-loaded Mg alloy upregulated reactive oxygen species (ROS) generation in bone tumor cells, resulting in mitochondrial dysfunction due to reduced membrane potential, thereby inducing bone tumor cell apoptosis. Furthermore, it was found that celastrol-induced autophagy in tumor cells inhibited cell apoptosis in the initial 6 h. After ≥12 h of culture, inhibition of the PI3K-Akt-mTOR signaling pathway was noted, resulting in excessive autophagy in tumor cells, finally causing cell apoptosis. The celatsrol-loaded Mg alloy also exhibited effective antitumor properties in a subcutaneous tumor model. In vitro tartrate-resistant acid phosphatase (TRAP) staining and gene expression results revealed that the modified Mg alloy reduced the viability of osteoclasts, inducing a potential pathway for the increased bone regeneration around the modified Mg alloy seen in vivo. Together, the results of our study show that the celatsrol-loaded Mg alloy might be a promising implant for treating OS.

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Osteosarcoma in Children: Not Only Chemotherapy

Cited by 17 publications

References 168 publications

Tumor microenvironment phenotypes and prognostic evaluation tools for osteosarcoma characterized by different prognostic outcomes and immunotherapy responses

Tumor microenvironment phenotypes and prognostic evaluation tools for osteosarcoma characterized by different prognostic outcomes and immunotherapy responses

Osteoporosis in Childhood Cancer Survivors: Physiopathology, Prevention, Therapy and Future Perspectives

Molecular Mechanism Underlying the Action of a Celastrol-Loaded Layered Double Hydroxide-Coated Magnesium Alloy in Osteosarcoma Inhibition and Bone Regeneration

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